Loss of function of the PTEN tumour suppressor, resulting in dysregulated activation of the phosphoinositide 3-kinase (PI3K) signalling network, is recognized as one of the most common driving events in prostate cancer development. The observed mechanisms of PTEN loss are diverse, but both homozygous and heterozygous genomic deletions including PTEN are frequent, and often accompanied by loss of detectable protein as assessed by immunohistochemistry (IHC). The occurrence of PTEN loss is highest in aggressive metastatic disease and this has driven the development of PTEN as a prognostic biomarker, either alone or in combination with other factors, to distinguish indolent tumours from those likely to progress. Here, we discuss these factors and the consequences of PTEN loss, in the context of its role as a lipid phosphatase, as well as current efforts to use available inhibitors of specific components of the PI3K/PTEN/TOR signalling network in prostate cancer treatment.
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February 2017
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Density-dependent scanning electron microscopy of calcifying vascular tissue (orange - calcification; green - collagen). Please see pp. 181-195 for more information. Image provided by Sergio Bertazzo.
Review Article|
January 05 2017
Prostate cancer, PI3K, PTEN and prognosis
Helen M. Wise;
Helen M. Wise
1Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, U.K.
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Miguel A. Hermida;
Miguel A. Hermida
1Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, U.K.
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Nicholas R. Leslie
1Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, U.K.
Correspondence: Nicholas R. Leslie (email n.r.leslie@hw.ac.uk)
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Publisher: Portland Press Ltd
Received:
June 15 2016
Revision Received:
November 12 2016
Accepted:
November 21 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (3): 197–210.
Article history
Received:
June 15 2016
Revision Received:
November 12 2016
Accepted:
November 21 2016
Citation
Helen M. Wise, Miguel A. Hermida, Nicholas R. Leslie; Prostate cancer, PI3K, PTEN and prognosis. Clin Sci (Lond) 1 February 2017; 131 (3): 197–210. doi: https://doi.org/10.1042/CS20160026
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